Apparatus and methods for the production of ultrasound contrast agents

Abstract

Disclosed is a method of making gas bubbles in a liquid, the bubbles having substantially uniform size suitable for responding to ultrasound or other diagnostic tools. Gas (P 2 ) is forced through one or more pores or nozzles, into the liquid (P 1 ), the nozzles or pores being of substantially uniform diameter, the flow of the gas being controlled to thereby cause the formation of substantially monodisperse gas bubbles in the liquid. Moreover, an apparatus is disclosed for making a suspension of gas bubbles in a liquid of a size suitable for responding to ultrasound or other diagnostic tools. Said apparatus comprises means for forcing a gas through an array of nozzles or pores into the liquid, the nozzles or pores being of substantially uniform diameter, and first means for controlling; a flow parameter of the gas so that gas is suspended as substantially monodisperse gas bubbles in the liquid. Furthermore a kit for preparing a dispersion of gas bubbles of substantially uniform size suitable for ultrasound purposes, is disclosed.

1 . A method of making gas bubbles in a liquid, the bubbles having substantially uniform size suitable for responding to ultrasound or other diagnostic tools, by forcing a gas through one or more pores or nozzles, into the liquid, the nozzles or pores being of substantially uniform diameter, the flow of the gas being controlled to thereby cause the formation of substantially monodisperse gas bubbles in the liquid. 
   
   
       2 . The method according to  claim 1  where the liquid is flowed past the nozzles or pores and the shear flow of the liquid is controlled to assist the formation of the substantially monodisperse gas bubbles in the liquid. 
   
   
       3 . The method according to  claim 1  wherein the pores or nozzles in an alumina, silicon, Shiraus Porous Glass or polymeric membranes. 
   
   
       4 . The method according to  claim 1  wherein the pore or nozzle diameters are smaller than 5 micrometer 
   
   
       5 . The method according to  claim 3  further comprising a hydrophobic surface on the gas input side of the porous membrane 
   
   
       6 . The method according to  claim 1  the liquid comprising amphiphilic molecules 
   
   
       7 . The method of  claim 6  the amphilic molecules being lipids and or biodegradable block-copolymers. 
   
   
       8 . An apparatus making a suspension of gas bubbles in a liquid of a size suitable for responding to ultrasound or other diagnostic tools, comprising:
 means for forcing a gas through an array of nozzles or pores into the liquid, the nozzles or pores being of substantially uniform diameter, and first means for controlling a flow parameter of the gas so that gas is suspended as substantially monodisperse gas bubbles in the liquid.   
   
   
       9 . A kit comprising compartments for a gas and a liquid, separated by a material of controlled porosity, through which the gas can be pressed into the liquid to yield a dispersion of gas bubbles of substantially uniform size suitable for ultrasound purposes. 
   
   
       10 . The kit as in  claim 9  that can be subjected to controlled flow of gas by the application of an external pressure 
   
   
       11 . The kit as in  claim 9  that can be subjected to controlled flow of liquid by an external pressure or a pump. 
   
   
       12 . The kit as in  claim 9  having flexible polymeric membranes (for the exertion of pressure) 
   
   
       13 . The kit as claimed in  claim 9  having flexible tubing to allow for volume changes by pressing the gas into the liquid. 
   
   
       14 . The kit as claimed in  claim 9  having an injection port to add additional components or extract the dispersion of gas bubbles. 
   
   
       15 . The kit as claimed in  claim 9  having a collection reservoir. 
   
   
       16 . The kit with a collection reservoir as claimed in  claim 9  oriented such that separation takes place on density. 
   
   
       17 . A kit as claimed in  claim 9  the kit being a cartridge that can be inserted in a table top type of apparatus that supplies external pressure, pumps the liquid and may supply the gas.